Poxviruses provide a unique experimental system for studying DNA replication. The ends of the linear double-stranded DNA genome consist of hairpin structures that may resemble telomeres of eukaryotic chromosomes. Enzymes and other proteins needed for DNA synthesis are encoded within the viral genome and replication occurs in the cytoplasmic compartment of infected cells. The DNA polymerase gene of vaccinia virus has been sequenced and the primary structure of the enzyme derived. Analysis of the DNA polymerase gene of a phosphonoacetate- resistant mutant virus revealed that a single nucleotide substitution results in drug resistance. This mutation may mark a part of the catalytic site of the enzyme. Studies on the mechanism of formation of the hairpin telomeres are continuing. Evidence has been obtained that the ends are formed by resolution of near perfect palindromes separating unit genomes in large concatemers. An in vivo transfection assay for the resolution reaction was developed and evidence for a specific sequence requirement within the palindrome has been obtained. Resolution has been obtained in vitro using a partially purified enzyme fraction from vaccinia virions. Rifampicin is known to prevent assembly of DNA-containing vaccinia virus particles. The gene conferring drug resistance of a mutant vaccinia has been mapped and sequenced.